title: Resistance against antimicrobial peptides is independent of Escherichia coli AcrAB, Pseudomonas aeruginosa MexAB and Staphylococcus aureus NorA efflux pumps.
abstract: The role of clinically important multidrug resistance (MDR) efflux pumps in bacterial resistance to various human antimicrobial peptides (AMPs), including cathelicidin LL-37, the alpha-defensins human neutrophil peptides (HNPs)-1-3 and HD-5 and the beta-defensins hBD-2 and -3, was investigated. AMP susceptibility testing was performed by killing assays and standard minimal inhibitory concentration assays. AMP susceptibility was determined in Escherichia coli and Pseudomonas aeruginosa strains overexpressing resistance-nodulation-cell division (RND)-type pumps AcrAB and MexAB, respectively, and in their pump-deficient parental strains. Furthermore, the impact of a member of the major facilitator (MF) efflux pump family was investigated in Staphylococcus aureus overexpressing NorA and in wild-type strains. The E. coli AcrAB and P. aeruginosa MexAB RND-type efflux pumps as well as the S. aureus NorA MF efflux pump were unable to confer resistance to AMPs. These findings do not support a critical role of MDR efflux pumps in the tested pathogens as a strategy to increase virulence by circumventing the antimicrobial action of innate defence AMPs.
authors.affiliation: Center for Infectious Diseases and Travel Medicine, Department of Medicine, University Hospital, Freiburg, Germany. siegbert.rieg@uniklinik-freiburg.de
authors.forename: Siegbert
authors.initials: S
authors.lastname: Rieg
authors.forename: Anja
authors.initials: A
authors.lastname: Huth
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.forename: Winfried V
authors.initials: WV
authors.lastname: Kern
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000096:biosynthesis; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D008074:Lipoproteins / Q000096:biosynthesis; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008074:Lipoproteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C083497:AcrA protein, E coli; C118598:MexA protein, Pseudomonas aeruginosa; C118597:MexB protein, Pseudomonas aeruginosa; C075040:NorA protein, Staphylococcus